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Title

A comparative study of drug delivery methods targeted to the mouse inner ear: bullostomy versus transtympanic injection

AuthorsVallecillo, Néstor; Celaya, Adelaida M. ; Contreras, Julio ; Cediel, Rafael ; Varela-Nieto, Isabel ; Murillo-Cuesta, Silvia
Issue Date2016
Citation3rd Symposium on Biomedical Research (2016)
AbstractDrug delivery to the inner ear is a challenge for the development of preclinical studies of novel drugs for the treatment of hearing loss (1). Two micro-surgery approaches for drug delivery to the inner ear, bullostomy and transtympanic injection were developed and compared in terms of impact on hearing, cochlear cytoarchitecture and expression of inflammatory cytokines. Bullostomy has been previously used for the delivery of TGFß inhibitors. Here we study the toxicity window of the oxysterol dendrogenin B (DDB) that has been proposed to be an ototoprotector targeting LXRs. Two month-old male C57BL/6J mice were operated by bullostomy or transtympanic injection. DDB at 7.7, 11.4, 45.6 and 76 mM was delivered close to the round window niche. Hearing was assessed with auditory brainstem responses before noise and 7, 14, and 28 days after surgery. Cochlear samples were taken 28 days after surgery and subjected to RT-qPCR analysis of inflammatory markers. Cochlear morphology was evaluated at the end of the experiment on hematoxylin-eosin stained paraffin sections. Neither surgical technique induced functional or morphological alterations in the cochlea. Local administration of DDB up to 45.6 mM caused no evident alterations but 76 mM was toxic, thus the toxicity threshold was established. Bullostomy was associated with a transitory increase in the expression levels of Il1b, Il6, Tnfa and Tgfb1 pro-inflammatory cytokines, whereas transtympanic injection reversibly up-regulated Il6 expression. Thus, these microsurgery methods represent a feasible and secure approach to test the ototoxicy of drugs as well as the efficiency of novel molecules. The transtympanic approach had the lowest impact.
DescriptionResumen del póster presentado al 3rd Symposium on Biomedical Research: "Advances and Perspectives in Neuroscience", celebrado en la Universidad Autónoma de Madrid el 22 de abril de 2016.
URIhttp://hdl.handle.net/10261/154145
Appears in Collections:(IIBM) Comunicaciones congresos
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